Little is known concerning the role of the carbohydrate structures present on functionally important B and T cell plasma membrane glycoproteins. The overall objectives of this project are the identification of specific immune cell protein glycoconjugates carrying immuno-regulatory sialic acids and, subsequently, the explication of these regulatory mechanisms at the molecular level. Previous studies have shown that neuraminidase treatment of resting B cells substantively enhances their capacity to activate resting T cells for proliferation and IL-2 secretion. In this study, the investigators will test the hypothesis that desialylation of currently unidentified B cell coreceptors and/or ligands is an essential step in B cell activation and recruitment of T cell help. Two specific aims are proposed. In the first aim, they will characterize as fully as possible the process of T cell activation by neuraminidase-treated resting B cells. They have hypothesized that neuraminidase-treated B cells are a mimic of activated B cells and that they activate T cells in an analogous fashion. The studies in this aim will 1) elucidate the sequence of events by which neuraminidase-treated resting B cells activate T cells; 2) evaluate the contribution of known costimulatory receptors and ligands to the process of T cell activation by neuraminidase-treated B cells. In the second aim, they propose to characterize the cell surface protein glycoconjugates desialylated by neuraminidase treatment and hyposialylated following B cell activation. The studies in this aim will 1) identify known costimulatory proteins whose sialic acid content is modified both by B cell activation and neuraminidase treatment; 2) evaluate the capacity of exogenous and endogenous sialyltransferases to effect recovery of the resting B cell phenotype; 3) characterize the extent of cell-surface glycoconjugate hyposialylation upon B cell activation by differing mechanisms; and 4) begin to characterize any unidentified glycoproteins whose cell surface sialic acid content is modified by both B cell activation and neuraminidase treatment.